Fludarabine treatment in B-cell chronic lymphocytic leukemia: response, toxicity and survival analysis in 47 cases

Background and Objective. Fludarabine monophosphate (FAMP) is a purine anal og with specific therapeutic activity in B-cell chronic lymphocytic leukemi a (CLL). Its current use as front-line therapy of CLL is still a matter of debate both because of the controversial results of the clinical trials so far reported and because of the toxicity profile of the drug. In order to c ontribute to clarifying the possible role of FAMP, we report a retrospectiv e analysis of the results obtained with the purine analog in CLL patients I n different phases of the disease. Design and Methods. Forty-seven patients affected by advanced CLL, 36% untr eated, 31.9% relapsed and 31.9% resistant, were treated with FAMP 25 mg/m(2 )/day, either for 4 days every 3 weeks in 29 cases, or for 5 days every 4 w eeks in 18. The median number of FAMP cycles was 6 (range 2-11). Response w as defined according to total tremor mass (TTM) score reduction and toxicit y was expressed according to WHO grading criteria. The median follow-up of the series was 13 months from the beginning of FAMP therapy. Results. Out of 47 evaluable patients the response rate was 74.4%, with 34% complete response (CR). The overall response rate was 94%, 80% and 46.6% i n untreated, relapsed and resistant cases, respectively; a significantly hi gher number of responses was associated with no previous treatment and numb er of FAMP cycles. Fifty-three percent of all cases and 58.8% of untreated ones did not experience any toxicity. Treatment-related side effects were m ainly autoimmune phenomena in untreated patients and infectious complicatio ns in treated ones. One heavily pre-treated patient died because of neurolo gic complications. Median time to re-treatment was 18 months (range 1-30) a nd was influenced by age and previous treatment. The overall median surviva l was 35.7 months with a significantly higher proportion of surviving cases among RAI 0-II stages, responders and patients receiving more than 5 FAMP cycles. Interpretation and Conclusions. The present report confirms the high effica cy of FAMP in previously pretreated cases with acceptable toxicity and enco urages its use as front-line treatment provided that the results of randomi zed trials demonstrate its superiority over conventional chemotherapy. The possible development of autoimmune phenomena should, however, be considered seriously. (C) 1999, Ferrata Storti Foundation.